Objective To compare the prognostic value of International Federation of Gynecology and Obstetrics (FIGO) 2009 and 2018 staging systems in surgical patients with small cell neuroendocrine carcinoma of the cervix (SCNEC). Methods We re-staged 64 surgical IB–IIA (FIGO 2009) SCNEC patients according to the FIGO 2018 system and refined stage IIIC of FIGO 2018 based on tumor local invasion. The prognostic factors were analyzed, and the advantages of FIGO 2018 were compared with 2009. Results The 5-year overall survival rate (OS) was 78.5% for stage I and 22.2% for stage II (FIGO 2009). In FIGO 2018, there was no difference between stage I and II, and the 5-year OS was 74.1%, 60.2%, and 0% for stage I/II, IIIC1, and IIIC2. After combining stage IIIC with the local invasion stage (T1 was limited to the cervix and vagina; T2 involved the parametrium; T3 involved the pelvic or abdominal cavity), the 5-year OS for stage IIICT1, IIICT2, and IIICT3 was 83.3%, 30.0%, and 0%, respectively. Conclusions For stage II SCNEC patients, FIGO 2009 underestimated the prognosis, while FIGO 2018 was more accurate. For stage IIIC, FIGO 2018 might be more individualized and accurate after combining stage IIIC with tumor local invasion.
Objective To screen for specific differentially expressed genes in small cell neuroendocrine carcinoma of the cervix (SCNEC) and to further explore their roles and mechanisms in tumor progression. Methods Differentially expressed genes in SCNEC compared with squamous cell carcinoma (SCC) and adenocarcinoma (AC) were screened by microarray and immunohistochemical analyses. The biological functions of the identified genes were examined in a SCNEC cell line using RNA interference and over-expression plasmid-transfection technologies. Co-expression network analysis and immunoprecipitation technology were used to explore the potential mechanisms. Results Compared with SCC and AC, UCHL1 (encoding ubiquitin C-terminal hydrolase L1) was identified as a specific differentially expressed gene in SCNEC, which was positively related to lymph node metastasis (LNM). Migration and invasion of SCNEC tumor cells were induced by UCHL1 over-expression and suppressed by UCHL1 down-regulation, as shown by scratch and transwell invasion assays. Co-expression network analysis suggested that Prospero homeobox protein 1 (PROX1) might interact with UCHL1, and in vivo immunoprecipitation and western blots verified that levels of ubiquitinated PROX1 were significantly decreased following UCHL1 overexpression. Conclusion UCHL1 is a potential biomarker of LNM in SCNEC. UCHL1 might promote SCNEC cell migration and invasion by reducing PROX1 ubiquitination.
Background Neuroendocrine cervical carcinoma (NECC) is a rare but aggressive malignancy with younger patients compared to other common histology types. This study aimed to evaluate the impacts of ovarian preservation (OP) on the prognosis of NECC through machine learning. Methods Between 2013 and 2021, 116 NECC patients with a median age of 46 years received OP or bilateral salpingo-oophorectomy (BSO) and were enrolled in a retrospective analysis with a median follow-up of 41 months. The prognosis was estimated using Kaplan–Meier analysis. Random forest, LASSO, stepwise, and optimum subset prognostic models were constructed in training cohort (randomly selected 70 patients) and tested in 46 patients through receiver operator curves. Risk factors for ovarian metastasis were identified through univariate and multivariate regression analyses. All data processing was carried out in R 4.2.0 software. Results Among 116 patients, 30 (25.9%) received OP and showed no significantly different OS compared with BSO group (p = 0.072) and got better DFS (p = 0.038). After construction of machine learning models, the safety of OP was validated in lower prognostic risk group (p > 0.05). In patients ≤ 46 years, no impacts of OP were shown for DFS (p = 0.58) or OS (p = 0.67), and OP had no impact on DFS in different relapse risk population (p > 0.05). In BSO group, regression analyses showed that later stage, para-aortic LNM, and parametrial involvement were associated with ovarian metastasis (p < 0.05). Conclusions Preserving ovaries had no significant impact on prognosis in patients with NECC. OP should be considered cautiously in patients with ovarian metastasis risk factors.
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